TNFAIP1

Chr 17

TNF alpha induced protein 1

Also known as: B12, B61, BTBD34, EDP1, hBACURD2

NCBI Gene: 7126ENSG00000109079UniProt: Q13829

This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein endothelial cells. Studies of a similar gene in mouse suggest that the expression of this gene is developmentally regulated in a tissue-specific manner. [provided by RefSeq, Jul 2008]

1
Active trials
52
ClinVar variants
6
Pathogenic / LP
1.5
Missense Z
0.64
LOEUF
4
Pubs (2 yr)
Clinical Summary— TNFAIP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 44 VUS of 52 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.135
Z-score 2.51
OE 0.28 (0.14–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.53Z-score
OE missense 0.70 (0.61–0.80)
143 obs / 204.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.14–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.61–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 4 / 14.2Missense obs/exp: 143 / 204.8Syn Z: -0.11

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS44
Benign2
5
Pathogenic
1
Likely Pathogenic
44
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
42
2
0
44
Likely Benign
0
0
0
0
0
Benign
0
0
1
1
2
Total0429152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNFAIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The CRL3(BTBD9) E3 ubiquitin ligase complex targets TNFAIP1 for degradation to suppress cancer cell migration.
Li L et al.·Signal Transduct Target Ther
2020
Tumor necrosis factor α-induced protein 1 as a novel tumor suppressor through selective downregulation of CSNK2B blocks nuclear factor-κB activation in hepatocellular carcinoma.
Xiao Y et al.·EBioMedicine
2020
STAT3 mediates ECM stiffness-dependent progression in ovarian cancer.
Chenchen S et al.·Mol Cell Biochem
2025
Circ_0002945 functions as a competing endogenous RNA to promote Aβ(25-35)-induced endoplasmic reticulum stress and apoptosis in SK-N-SH cells and human primary neurons.
Li G et al.·Brain Res
2022
Characterization of methylation profile in biofluid cell-free DNA and identification of differentially methylated genes for phenotypic representations in Parkinson's disease.
Zhu A et al.·Clin Neurol Neurosurg
2025
[Differential expression of taxol resistance and taxol resistance reversal related genes in nasopharyngeal carcinoma by cDNA microarray].
Peng X et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
TNFAIP1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the LEENE/FoxO1/ABCA1 pathway.
Xu C et al.·J Physiol Biochem
2024
HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells.
Lv D et al.·In Vivo
2024
Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination.
Wang W et al.·Cell Commun Signal
2023Open Access
Screening of Tnfaip1-Interacting Proteins in Zebrafish Embryonic cDNA Libraries Using a Yeast Two-Hybrid System.
Huang S et al.·Curr Issues Mol Biol
2023Open AccessFunctional
Knocking down TNFAIP1 alleviates inflammation and oxidative stress in pediatric pneumonia through PI3K/Akt/Nrf2 pathway.
Chen J et al.·Allergol Immunopathol (Madr)
2023
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
CRISPR/Cas9-Mediated Knockout of tnfaip1 in Zebrafish Plays a Role in Early Development
Huang S et al.·Genes (Basel)
2023Functional
Inhibition of TNFAIP1 ameliorates the oxidative stress and inflammatory injury in myocardial ischemia/reperfusion injury through modulation of Akt/GSK-3beta/Nrf2 pathway.
Wen L et al.·Int Immunopharmacol
2021
The role of TNF-alpha induced protein 1 in the activation of pro-apoptotic proteins.
Tang X et al.·Hum Cell
2021
TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH-SY5Y Cells by Binding to RhoB.
Xiao Y et al.·J Mol Neurosci
2021
Downregulation of TNFAIP1 alleviates OGD/R-induced neuronal damage by suppressing Nrf2/GPX4-mediated ferroptosis
Xiong L et al.·Exp Ther Med
2022
MiR-93 alleviates DEHP plasticizer-induced neurotoxicity by negatively regulating TNFAIP1 and inhibiting ubiquitin-mediated degradation of CK2beta.
Qiu F et al.·Food Chem Toxicol
2023
Circ0001320 inhibits lung cancer cell growth and invasion by regulating TNFAIP1 and TPM1 expression through sponging miR-558.
Mao Y et al.·Hum Cell
2021
Top 7 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Concussion, BrainMild Traumatic Brain Injury

Risk Stratification in Children With Concussion

RECRUITING
NCT05825027Duke UniversityStarted 2023-05-23

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients